Interstitial lung diseases during treatment with sunitinib or mTOR inhibitors in metastatic renal cell carcinoma.

420 Background: Targeted therapies are the mainstay for metastatic renal cell carcinoma (mRCC) treatment. Interstitial lung disease (ILD) represents an adverse event (AE) of such therapies while its incidence and management is poorly defined. Here, the experience on ILD with targeted agents in mRCC is reported. Methods: Retrospective analysis of mRCC patients receiving sunitinib, everolimus, or temsirolimus at three German tertiary centers between January 2006 and August 2009 was performed, accessing ILD incidence, management, and outcomes. Results: In total 26 ILD patients were identified out of 306 mRCC patients (8.5%) treated with targeted therapies. Median treatment duration to ILD diagnosis was 3.8 (range 0.98-21.5) months. ILD occurred in 6 of 204 sunitinib treated patients (2.9%), and in 20 of 102 mTOR inhibitor (mTORi) treated patients (19.6%). Cough represents the predominant symptom (69.2%, n=18). Chest CTs revealed 4 patterns: interstitial (n=13), nodular (n=3), ground glass opacities (n=8), or complex patterns (n=2). Pulmonary function tests (PFT) illustrates frequently a restrictive disorder (n=9), often accompanied by a diminished diffusion capacity (n=8). In 53.8% (n=14) a bronchoscopy with broncho-alveolar-lavage (BAL) was performed (lymphocytic cellularity n=6, eosinophilic cellularity n=4). Dose reduction (42.3%, n=11), temporary interruption (46.2%, n=12), or treatment withdrawal (53.8%, n=14) occurred frequently. Nine patients (34.6%) received steroids. Continuation of targeted therapies was maintained in 65.4% (n=17). No patient died from ILD. Conclusions: ILD represents a frequent AE with targeted therapies and also occurs in sunitinib treated patients. For diagnosis of ILD chest CTs are mandatory, whereas PFT and BALs are important subsidiary tools. Clinical relevance of ILD may vary and management of ILD ranges from watch and wait to termination of treatment and steroid pulse therapy. Severe complaints were more frequently associated with eosinophilic BAL, often required an aggressive treatment. However, in most patients, temporary interruption and/or dose reduction with subsequent continuation of targeted therapy remain sufficient to manage ILD.

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Evolving Treatment Paradigm in Metastatic Renal Cell Carcinoma

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_174469 ◽

2017 ◽

pp. 319-329

Author(s):

David M. Gill ◽

Neeraj Agarwal ◽

Ulka Vaishampayan

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Targeted Therapies ◽

Renal Cell ◽

Kinase Inhibitors ◽

Kinase Inhibitor ◽

Checkpoint Inhibitors ◽

Mtor Inhibitors ◽

Treatment Paradigm

The treatment paradigm for advanced and metastatic renal cell carcinoma (mRCC) has evolved rapidly since the arrival of targeted therapies and novel immunotherapies. mRCC was previously treated only with cytokines. However, discoveries of mutations affecting the von Hippel–Lindau tumor suppressor gene (leading to increased expression of VEGF and hypoxia inducible factor/HIF-1) and of deregulations in the phosphatidylinositol-3 kinase/AKT/mTOR pathway (resulting in tumor angiogenesis, cell proliferation, and tumor growth) have led to the development of numerous targeted therapies. The U.S. Food and Drug Administration (FDA) has thus approved a total of nine targeted therapies since 2005, including VEGF tyrosine kinase inhibitors (sunitinib, pazopanib, axitinib, sorafenib, and lenvatinib), a monoclonal antibody targeting VEGF (bevacizumab), mTOR inhibitors (temsirolimus and everolimus), and a multityrosine kinase inhibitor (cabozantinib). Furthermore, the development of immune checkpoint inhibitors has again shifted the mRCC therapeutic landscape with the FDA’s approval of nivolumab. Herein, we discuss the unprecedented changes in the field of clear cell histology mRCC in both the first-line and salvage settings, and we also discuss future therapies and recommend a treatment paradigm on sequencing of these agents.

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Correlation Between the Tyrozinkinazine Inhibitor Sunitinib - Dose, Schedule of Administration and Adverse Events

Revista de Chimie ◽

10.37358/rc.17.7.5737 ◽

2017 ◽

Vol 68 (7) ◽

pp. 1652-1659

Author(s):

Dana Lucia Stanculeanu ◽

Raluca Ioana Mihaila ◽

Daniela Zob ◽

Oana Catalina Toma ◽

Raluca Ioana Mihaila ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Adverse Events ◽

Cell Carcinoma ◽

Dose Reduction ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitor ◽

Dose Schedule ◽

Prophylactic Measures ◽

Hand Foot Syndrome

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, has demonstrated survival benefit in patients with metastatic renal cell carcinoma (mRCC) and is generally well tolerated with most adverse events, manifesting as mild to moderate in severity. The most frequent related adverse events include hand-foot syndrome (HFS), hypertension, proteinuria, cardiac toxicities, myelosuppression, fatigue/asthenia, hypothyroidism, diarrhea and hepatotoxicity. The study aims to determine incidence of adverse events among patients with metastatic renal cell carcinoma (mRCC) treated Sunitinib within five years from 2010 to 2015 and comparing the results with data from literature. The study included a total of 56 patients treated with Sunitinib, with a dose of 50 mg (Schedule 4/2). Due to adverse events and individual safety and tolerability, at the indication of the personal clinician, 11 patients needed dose reduction, with a continuous dose of 37.5 mg, daily and 28 patients continued the dose of 50 mg taken daily, on a different schedule (2/1 schedule). The most important toxicities were anemia, leukopenia, thrombocytopenia, gastrointestinal effects (diarrhea), fatigue and hypertension. After dose reduction or modified schedule the incidence of the most frequent toxicities (HFS, leukopenia, thrombocytopenia and fatigue) decreased, but hypertension was still observed in 30% of patients. The results are similar with data from literature. Early identification of individuals at risk and monitoring patients during Sunitinib treatment is very important and it can facilitate early intervention with prophylactic measures or supportive treatment, thus increasing quality of life and adherence to treatment. Further studies need to establish which targeted population can benefit the most from adjusted regimens and to correlate them with prognostic factors for survival.

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